A South African family with oculopharyngeal muscular dystrophy : clinical and molecular genetic characteristics

摘要

Autosomal dominantly inherited oculopharyngeal muscular dystrophy (OPMD) is caused by a trinucleotide repeat expansion in exon 1 of thepolyadenylate binding protein nuclear 1 (PABPN1) gene on chromosome 14q. A large family with OPMD was recently identified in Pretoria,South Africa (SA). Molecular studies revealed a (GCG)11(GCA)3GCG or (GCN)15 mutant allele. The (GCN)15 mutation detected in this familyhas been described previously in families from Uruguay and Mexico as a founder effect. To our knowledge, this is the first report of an SAAfrikaner family with molecularly confirmed OPMD. The proband, a 64-year-old woman, presented to the neurology outpatient department atSteve Biko Academic Hospital, Pretoria. A sibship of 18 individuals was identified, of whom eight had OPMD. Four patients were interviewedand examined clinically, and electromyographic studies were performed. Molecular analysis of the PABPN1 gene was performed by polymerasechain reaction amplification and direct sequencing of exon 1 in three of the patients. Patients presented with ptosis, external ophthalmoplegia,dysphagia, dysarthria and mild proximal weakness. High foot arches and absent ankle reflexes raised the possibility of peripheral neuropathy,but electromyography showed only mildly low sensory amplitudes, and myopathic units in two patients.